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Post-Cardiac Arrest Patients: Who Survives Cognitively Intact After Hypothermia?

Talan, Jamie

doi: 10.1097/01.NT.0000427246.59024.57
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HYPOTHERMIA THERAPY: Cooling is induced with two liters of chilled saline at 4 degrees C; ice bags are placed on the groin and under the armpits, and cooling wraps are used around the chest and legs

HYPOTHERMIA THERAPY: Cooling is induced with two liters of chilled saline at 4 degrees C; ice bags are placed on the groin and under the armpits, and cooling wraps are used around the chest and legs

In a small retrospective study, investigators found that patients with post-cardiac arrest syndrome who had seizure activity, specifically status epilepticus (SE), had poorer outcomes than those who had no evidence of seizure activity on the continuous EEG monitoring.

Dozens of post-cardiac arrest patients who received therapeutic hypothermia and continuous EEG monitoring at the University of Pennsylvania are helping unravel a puzzle about who is more likely to survive and walk out of the hospital cognitively intact.

The retrospective study, published last year in Resuscitation, suggests that patients who had seizure activity, specifically status epilepticus (SE), had poorer outcomes than those who had no evidence of seizure activity on the continuous EEG monitoring. But the study was small — 38 patients — and the findings also raise another possibility: that treating status epilepticus earlier and more aggressively may improve outcomes.

There are still a lot of questions about which patients are more likely to survive, which is why David Gaieski, MD, assistant professor of emergency medicine at the Hospital of the University of Pennsylvania, and his colleagues have been mining their therapeutic hypothermia data to figure out which patients are more likely to benefit from the cooling technique. During the procedure, cooling is induced with two liters of chilled saline at 4 degrees C; ice bags are placed on the groin and under the armpits, and cooling wraps are used around the chest and legs. Some hospitals cool the body from the inside out with cooling solutions in intravascular catheters. Patients remain cooled at 33 degrees C. for 24 hours and then are slowly rewarmed.

They started their hypothermia program in 2004 and cooled their first patient the following year. Over 300 post-cardiac arrest patients have received therapeutic hypothermia at Penn. Before the program got under way, about 22 percent of comatose post-cardiac arrest patients survived to hospital discharge. Today, it is 46 percent. And a greater number of survivors — 78 percent — are leaving the hospital neurologically intact, said Dr. Gaieski. What's more, others who received therapeutic hypothermia began showing clinical improvement over the six-month period following discharge such that approximately 90 percent of survivors are neurologically intact at six months.

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Looking back on the charts of 38 people, Dr. Gaieski; Ram Mani, MD; and their colleagues identified nine patients with electrographic seizures. Five of the nine patients had seizures within the first 24-hours. And 45 percent (17 of 38 patients) had had evidence of epileptiform activity during the first 24-hours post-cardiac arrest.

While the neurologists read the continuous EEG twice a day, the treatment of the seizure activity was left up to the patient's primary team. That said, the outcome of those with seizures was poor, Dr. Gaieski said.

Twenty of the 38 patients died during their hospital stay: seven of nine patients (78 percent) with seizures and 13 of 29 (45 percent) of those without seizures. There were no good neurological outcomes in the seizure group while 12 of 29 (41 percent) in the group without seizures had good neurological outcomes at discharge. Six of the nine patients with seizures were withdrawn from ventilator support compared with six of 29 (21 percent) of those without any sign of seizure activity.

“Clinicians used to think that seizures were associated with rewarming but our study suggests that this is not true,” said Dr. Gaieski. He contends that seizures are a sign of a more injured brain and are associated with worse outcomes. “But the presence of seizures is neither sensitive nor specific enough to be a definitive marker in isolation,” he said. “A large percentage of people without seizures also doesn't recover or leave the hospital.”

The study raises a new set of questions about optimal post-arrest care including the greater use of continuous EEGs, whether prophylactic anti-epileptic drugs started immediately after arrest would decrease the percentage of patients who develop seizures, how aggressive the treatment of status epilepticus should be, and whether or not to extend the period of time of cooling time to give the more injured brain a longer time to heal.

He said that a study randomizing comatose post-cardiac arrest patients with seizures into different treatment groups could ultimately answer the question of whether getting seizures under control changes the outcomes for survivors.

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In an editorial in the same issue, Romergryko Geocadin, MD, and Eva Ritzl, MD, neurologists at Johns Hopkins University, said that “as we attempt to better understand epileptiform activity, seizures and status epilepticus in post-cardiac arrest patients, we realize that the problems are not limited to the timing of EEG testing or the recognition of seizures, but also the lack of proven effective treatments for seizures and SE in PCAS [post-cardiac arrest syndrome].

“There are two ways of looking at seizures and SEs in PCAS: as a prognosticator for poor outcome, which will almost guarantee a self-fulfilling prophecy, or as a challenge to further develop novel diagnostic approaches and therapies to improve outcomes,” they wrote.

Dr. Geocadin told Neurology Today that therapeutic hypothermia “has changed the way we think about brain injury. We thought it was futile. It is not.”

He sees this study as a wake-up call for neurologists to get involved right when the patient survives the cardiac arrest and therapeutic cooling begins. A routine EEG only showed seizures in eight percent but that jumped to 23 percent when done continuously. Many hospitals still do not have the resources for continuous EEG, Dr. Geocadin said.

“We need to study this more and attempt to control seizures early on,” he added. “How can we say that seizures are a problem that predicts poor outcome if we have no good treatments to control them?”

“The next essential component of post-resuscitation care is continuous EEG,” said Stephan Mayer, MD, a professor of neurology and neurosurgery and director of the neuro critical care unit at Columbia University Medical Center. “If you could detect and control seizures could you alter the outcome? We just don't know. What we do know is that seizures cause secondary injury to the brain.”

Dr. Mayer and others interviewed said “neurologists need to be called immediately and be part of the resuscitation team.” He added that this study shows that 25 percent of patients are seizing and neurologists need to be on hand to read the EEG and start treatment if the patient is seizing.

“I applaud the paper,” he added. “It is a clarion call for neurologists. These patients are salvageable and acute management can make a tremendous difference. There are no other specialists with this skill set to get the EEG going and treat seizures when they are identified.”

Vanja Douglas, MD, a neuro-hospitalist and assistant professor of clinical neurology at University of California, San Francisco, agrees. They have been cooling post-cardiac arrest patients since 2003. “Many physicians feel that status epilepticus in these patients is a poor prognosis and this may influence their decision about whether they continue care or withdrawal life support. We don't have the data to know whether treating seizures aggressively will change the outcome, but these findings suggest that it is something we need to study.”

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The first studies on therapeutic hypothermia were published in the New England Journal of Medicine in 2002. In one of the studies, conducted in Europe, 75 of 136 patients (55 percent) resuscitated from cardiac arrest due to ventricular fibrillation had a favorable neurological outcome with the cooling treatment. In comparison, 55 of 137 patients (39 percent) had a favorable outcome with standard supportive care alone. Standard care includes reviving the patient and keeping his or her blood pressure and heart rhythm in a normal range. A smaller single-center study from Australia showed similar results.

On the heels of these papers, the American Heart Association and the International Liaison Committee on Resuscitation agreed that medical teams ought to be cooling the body following sudden cardiac arrest.

—Jamie Talan

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• Mani R, Schmitt SE, Gaieski DF, et al. The frequency and timing of epileptiform activity on continuous electroencephalogram in comatose post-cardiac arrest syndrome patients treated with therapeutic hypothermia. Resuscitation 2012;83(7):840–847. E-pub 2012 Feb 23.
    • Geocadin RG, Ritzl EK. Editorial: Seizures and status epilepticus in post cardiac arrest syndrome: Therapeutic opportunities to improve outcome or basis to withhold life-sustaining therapies? Resuscitation 2012;83(7):791–792.
      Neurology Today archive on therapeutic hypothermia:
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